Ravulizumab for Kidney Transplant

(AWAKE Trial)

Recruiting at 126 trial locations

Overseen By Alexion Pharmaceuticals, Inc. (Sponsor)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alexion Pharmaceuticals, Inc.

Disqualifiers: Acute kidney injury, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

450 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called ravulizumab to determine if it helps people recover faster after a kidney transplant. Specifically, it aims to reduce the need for dialysis, which filters blood when kidneys cannot. Participants will receive either ravulizumab or a placebo (a treatment with no active drug) to compare results. The trial is best suited for individuals with end-stage kidney disease who are about to receive a transplant from certain types of deceased donors. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

Is there any evidence suggesting that ravulizumab is likely to be safe for humans?

Research has shown that ravulizumab is generally well-tolerated by patients. In various studies, some patients experienced side effects, but most were unrelated to the treatment. For instance, one study identified 23 side effects in 19 patients, with none linked to ravulizumab. Another study reported 21 side effects in 15 patients, again with no connection to the treatment.

In a separate analysis, only 3 out of 20 side effects were linked to ravulizumab, including mild issues like headaches and tiredness. Importantly, no unexpected side effects emerged.

Ravulizumab is also approved for other conditions, indicating a known safety record. However, individual experiences can vary, so discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ravulizumab is unique because it targets the complement system, specifically the C5 protein, which plays a role in the body’s immune response. Unlike standard treatments for kidney transplant rejection that often involve broad immunosuppressants, ravulizumab provides a more targeted approach, potentially reducing the risk of infections and other side effects associated with generalized immune suppression. Researchers are excited about ravulizumab because it offers the promise of better long-term outcomes for transplant patients by minimizing organ rejection while maintaining the body's ability to fight infections.

What evidence suggests that ravulizumab might be an effective treatment for reducing the severity of DGF?

Research has shown that ravulizumab may benefit kidney transplant patients, particularly those with atypical hemolytic uremic syndrome (aHUS), a condition that causes blood clots in small blood vessels. In previous studies, 72.2% of patients who switched from eculizumab to ravulizumab experienced significant symptom improvement. These studies found no unexpected side effects. Ravulizumab targets certain proteins in the immune system to help protect blood vessels from damage. In this trial, participants will receive either ravulizumab or a placebo to study the drug's effect on delayed graft function (DGF) after kidney transplants. While these results are promising for patients with aHUS, the drug's effect on DGF remains under investigation. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults at high risk of delayed graft function (DGF) after receiving a kidney transplant from a deceased donor. Specific eligibility details are not provided, but typically participants must meet certain health standards and not have conditions that could interfere with the study.

Inclusion Criteria

I am eligible for a kidney transplant from a high-risk donor.

I am eligible for a kidney transplant from a donor after circulatory death.

I am on dialysis for end-stage kidney disease.

Exclusion Criteria

My kidney donor matches specific criteria.

I have been diagnosed with severe acute kidney injury.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ravulizumab or placebo intravenously to evaluate efficacy in reducing delayed graft function

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on time to freedom from dialysis

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ravulizumab

Trial Overview The study aims to test if Ravulizumab can reduce the severity of DGF compared to a placebo. It measures how long it takes patients to be free from dialysis post-transplant. Participants will be randomly assigned to receive either Ravulizumab or placebo in a double-blind manner.

How Is the Trial Designed?

Group I: Ravulizumab Experimental Treatment 1 Intervention

Participants will receive an IV dose of ravulizumab.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive an IV dose of placebo.

Who Is Running the Clinical Trial?

Alexion Pharmaceuticals, Inc.

Lead Sponsor

Trials

267

Recruited

141,000+

Dr. Alberto R. Martinez

Alexion Pharmaceuticals, Inc.

Chief Medical Officer since 2010

MD from University of Sao Paulo

Marc Dunoyer

Alexion Pharmaceuticals, Inc.

Chief Executive Officer since 2021

PhD in Molecular Biology

Published Research Related to This Trial

In a trial involving 80 kidney transplant recipients with preformed donor-specific antibodies, eculizumab significantly reduced the treatment failure rate to 8.8%, compared to an expected 40% with standard care, indicating its efficacy in preventing acute antibody-mediated rejection (AMR).

Eculizumab was well tolerated with no new safety concerns, and at 36 months, the graft and patient survival rates were 83.4% and 91.5%, respectively, suggesting it is a safe option for prophylaxis against AMR in kidney transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of eculizumab for the prevention of antibody-mediated rejection after deceased-donor kidney transplantation in patients with preformed donor-specific antibodies. Glotz, D., Russ, G., Rostaing, L., et al.[2023]

Ravulizumab is an effective treatment for atypical hemolytic uremic syndrome (aHUS), resolving thrombotic microangiopathy in 54% of adult and 78% of pediatric treatment-naïve patients within 26 weeks, making it a promising option for both groups.

With a maintenance dosage of once every 4-8 weeks, ravulizumab offers a more convenient treatment schedule compared to its predecessor eculizumab, which requires dosing every 2-3 weeks, while maintaining a good safety profile with common side effects like headache and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ravulizumab: A Review in Atypical Haemolytic Uraemic Syndrome. Syed, YY.[2022]

Ravulizumab is a monoclonal antibody that inhibits complement C5, effectively preventing cell lysis in conditions like paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), and received its first approval in the USA in December 2018 for treating adults with PNH.

The drug has been developed using technology to extend its half-life, allowing for less frequent dosing, and is currently being evaluated for additional uses in myasthenia gravis and IgA nephropathy, as well as a subcutaneous formulation for easier administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ravulizumab: First Global Approval. McKeage, K.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40875209/

Effectiveness and Safety of Switching to Ravulizumab From ... Effectiveness and safety outcomes were assessed in kidney transplant recipients with aHUS who switched to ravulizumab from eculizumab up to September 2, 2024.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2468024924017960

Global aHUS Registry Analysis of Patients Switching to ... During ravulizumab treatment, 20 AEs occurred in 13 patients, with no unexpected AEs and only 3 treatment-related AEs (infusion reaction, headaches, and fatigue) ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/2613/530156/Real-World-Effectiveness-of-Ravulizumab-Among

Real-World Effectiveness of Ravulizumab Among Adults with ... Complete TMA response was achieved in 26 patients (72.2%) within 18 months of eculizumab initiation and early switch to ravulizumab. Conclusion: ...

4. journals.lww.com journals.lww.com/jasn/fulltext/2024/10001/safety_and_effectiveness_of_switching_to.3549.aspx

Safety and Effectiveness of Switching to Ravulizumab from... This analysis from the Global aHUS Registry provides real-world evidence of the successful transition from ECU to RAV in KTx recipients with aHUS.

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/pdf/10.1111/ctr.70278

Effectiveness and Safety of Switching to Ravulizumab From ... Results: Overall, 38 patients received a kidney transplant before ravulizumab initiation; 27 patients with ≥3 months of ravulizumab treatment ...

6. bmcnephrol.biomedcentral.com bmcnephrol.biomedcentral.com/articles/10.1186/s12882-024-03638-3

Clinical efficacy and safety of switching from eculizumab to ... Switching to ravulizumab was safe and efficient resulting in sustained hematological stability and preservation of renal function.